tbuckley/cabot-search huggingface dataset:
Acute Kidney Injury Among Children Likely Associated with Diethylene Glycol–Contaminated Medications — The Gambia, June–September 2022
Authors: Parsa Bastani, Anna Jammeh, Frederica Lamar, Jason H. Malenfant, Peter Adewuyi, Alyson M. Cavanaugh, Kimberly Calloway, Carolyn Crisp, Nuha Fofana, T. Christy Hallett, Amadou Jallow, Uzoamaka Muoneke, Momodou Nyassi, Jerry Thomas, Alyssa Troeschel, Ellen Yard, Michael Yeh, Mustapha Bittaye
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

On July 26, 2022, a pediatric nephrologist alerted The Gambia's Ministry of Health (MoH) to a cluster of cases of acute kidney injury (AKI) among young children at the country's sole teaching hospital, and on August 23, 2022, MoH requested assistance from CDC. CDC epidemiologists arrived in The Gambia, a West African country, on September 16 to assist MoH in characterizing the illness, describing the epidemiology, and identifying potential causal factors and their sources. Investigators reviewed medical records and interviewed caregivers to characterize patients' symptoms and identify exposures. The preliminary investigation suggested that various contaminated syrup-based children's medications contributed to the AKI outbreak. During the investigation, MoH recalled implicated medications from a single international manufacturer. Continued efforts to strengthen pharmaceutical quality control and event-based public health surveillance are needed to help prevent future medication-related outbreaks.
Age as a risk factor for surgical site infections: German surveillance data on total hip replacement and total knee replacement procedures 2009 to 2018
Authors: Peter Bischoff, Tobias Siegfried Kramer, Christin Schröder, Michael Behnke, Frank Schwab, Christine Geffers, Petra Gastmeier, Seven Johannes Sam Aghdassi
Journal: Eurosurveillance (2023)

Background Older age is frequently cited as a risk factor for healthcare-associated infections in general, and surgical site infections (SSIs) specifically. Aim We aimed to investigate the correlation between age and SSI occurrence. Methods Data on total hip replacement (THR) and total knee replacement (TKR) surgeries and resulting SSIs documented in the German national surveillance network from a 10-year period from 2009 to 2018 were selected for analysis. SSI rates and adjusted odds ratios (AOR) were calculated and a multivariable analysis to determine risk factors for SSI occurrence was conducted. Results A total of 418,312 THR procedures resulting in 3,231 SSIs, and 286,074 TKR procedures with 1,288 SSIs were included in the analyses. For THR, SSI rates were higher in older age groups when compared with the reference age group of 61–65 years. A significantly higher risk was observed in the 76–80 years age group (AOR: 1.21, 95% CI: 1.05–1.4). An age of ≤ 50 years was associated with a significantly lower SSI risk (AOR: 0.64, 95% CI: 0.52–0.8). For TKR, a similar correlation was observed, with the exception of the youngest age group (≤ 52 years), which was shown to have an SSI risk equal to that of the knee prosthesis reference age group (78–82 years). Conclusion A strong correlation between increasing age and SSI occurrence was observed for both procedure types. The results of our analyses provide a basis to consider future targeted SSI prevention measures for different age groups.
<scp>Non‐Redundant</scp> Roles of T Cell Costimulation Pathways in Inflammatory Arthritis Revealed by Dual Blockade of <scp>ICOS</scp> and <scp>CD28</scp> with Acazicolcept (<scp>ALPN</scp>‐101)
Authors: Stacey R. Dillon, Lawrence S. Evans, Katherine E. Lewis, Susan Debrot, Tiffany C. Blair, Sherri Mudri, Kayla Kleist, Steven D. Levin, Janhavi G. Bhandari, Logan Garrett, Martin F. Wolfson, Pamela M. Holland, Mark W. Rixon, Stanford L. Peng
Journal: Arthritis & Rheumatology (2023)

CD28 and inducible T cell costimulator (ICOS) appear to have nonredundant roles in T cell activation and adaptive immunity. We undertook this study to characterize in vitro and in vivo the therapeutic potential of acazicolcept (ALPN-101), an Fc fusion protein of a human variant ICOS ligand (ICOSL) domain designed to inhibit both CD28 and ICOS costimulation, in inflammatory arthritis.Acazicolcept was compared in vitro with inhibitors of either the CD28 or ICOS pathways (abatacept and belatacept [CTLA-4Ig], prezalumab [anti-ICOSL monoclonal antibody]) in receptor binding and signaling assays, and in a collagen-induced arthritis (CIA) model. Acazicolcept was also compared in cytokine and gene expression assays of peripheral blood mononuclear cells (PBMCs) from healthy donors or rheumatoid arthritis (RA) or psoriatic arthritis (PsA) patients stimulated with artificial antigen-presenting cells (APCs) expressing CD28 and ICOS ligands*.Acazicolcept bound CD28 and ICOS, prevented ligand binding, and inhibited human T cell functional interactions, matching or exceeding the activity of CD28 or ICOS costimulatory single-pathway inhibitors tested individually or in combination. Acazicolcept administration significantly reduced disease in the CIA model and more potently than abatacept. Acazicolcept also inhibited proinflammatory cytokine production from stimulated PBMCs in cocultures with artificial APCs and demonstrated unique effects on gene expression distinct from those induced by abatacept, prezalumab, or a combination of both.Both CD28 and ICOS signaling play critical roles in inflammatory arthritis. Therapeutic agents such as acazicolcept that coinhibit both ICOS and CD28 signaling may mitigate inflammation and/or disease progression in RA and PsA more effectively than inhibitors of either pathway alone.
US public investment in development of mRNA covid-19 vaccines: retrospective cohort study
Authors: Hussain S Lalani, Sarosh Nagar, Ameet Sarpatwari, Rachel E Barenie, Jerry Avorn, Benjamin N Rome, Aaron S Kesselheim
Journal: BMJ (2023)

To estimate US public investment in the development of mRNA covid-19 vaccines.Retrospective cohort study.Publicly funded science from January 1985 to March 2022.National Institutes of Health (NIH) Report Portfolio Online Reporting Tool Expenditures and Results (RePORTER) and other public databases. Government funded grants were scored as directly, indirectly, or not likely related to four key innovations underlying mRNA covid-19 vaccines-lipid nanoparticle, mRNA synthesis or modification, prefusion spike protein structure, and mRNA vaccine biotechnology-on the basis of principal investigator, project title, and abstract.Direct public investment in research and vaccine development, stratified by the rationale, government funding agency, and pre-pandemic (1985-2019) versus pandemic (1 January 2020 to 31 March 2022).34 NIH funded research grants that were directly related to mRNA covid-19 vaccines were identified. These grants combined with other identified US government grants and contracts totaled $31.9bn (£26.3bn; €29.7bn), of which $337m was invested pre-pandemic. Pre-pandemic, the NIH invested $116m (35%) in basic and translational science related to mRNA vaccine technology, and the Biomedical Advanced Research and Development Authority (BARDA) ($148m; 44%) and the Department of Defense ($72m; 21%) invested in vaccine development. After the pandemic started, $29.2bn (92%) of US public funds purchased vaccines, $2.2bn (7%) supported clinical trials, and $108m (<1%) supported manufacturing plus basic and translational science.The US government invested at least $31.9bn to develop, produce, and purchase mRNA covid-19 vaccines, including sizeable investments in the three decades before the pandemic through March 2022. These public investments translated into millions of lives saved and were crucial in developing the mRNA vaccine technology that also has the potential to tackle future pandemics and to treat diseases beyond covid-19. To maximize overall health impact, policy makers should ensure equitable global access to publicly funded health technologies.
Highlights from Recent Cancer Literature
Journal: Cancer Research (2023)

Despite hundreds of trials examining the combination of radiotherapy with immunotherapy, evidence for synergy as well as predictive biomarkers are lacking.Spurr and colleagues conducted a trial to examine the efficacy of the combination of immunotherapy plus multisite ablative radiotherapy in non-small cell lung cancer patients.Genomic and transcriptomic analyses of baseline and on-treatment biopsies demonstrated that concurrent radiation and immunotherapy increased the adaptative immune response while radiation alone decreased this response.Furthermore, high baseline aneuploidy predicted improved outcomes in patients treated with concurrent therapy.Expert Commentary: This study suggests that high tumor aneuploidy may be a biomarker of response to concurrent radiotherapy and immunotherapy and should be validated in future trials.
A patient-tailored approach for corticosteroid treatment in COVID-19: still not there yet
Authors: Mattia Nigro, James D. Chalmers, Stefano Aliberti
Journal: European Respiratory Journal (2023)

Three years after its first appearance, SARS-CoV-2 is still among the most troublesome respiratory viruses and the COVID-19 pandemic is still not under control globally [1]. A clear association between dysregulated inflammation and adverse clinical outcomes has been demonstrated in COVID-19 since the very beginning of the pandemic with the so-called "cytokine storm" advocated as the key pathogenetic mechanism in severe disease [2, 3]. The scientific community theorized the use of immunomodulating agents to control this process and, among them, systemic corticosteroids have been extensively used during the pandemic since their first evidence in reducing mortality in June 2020 [4]. International guidelines unanimously report moderate-to-strong recommendations in favour of corticosteroids for hospitalised COVID-19 patients with acute respiratory failure (ARF) based on moderate-to-high quality evidence [5–9].
Human Papillomavirus Vaccination Prevalence and Disproportionate Cancer Burden Among US Veterans
Authors: Smrithi Chidambaram, Su-Hsin Chang, Vlad C. Sandulache, Angela L. Mazul, Jose P. Zevallos
Journal: JAMA Oncology (2023)

This cross-sectional study examines the rate of HPV vaccination and the number eligible for this vaccination among younger veterans and civilians.
TFAM deficiency in dendritic cells leads to mitochondrial dysfunction and enhanced antitumor immunity through cGAS-STING pathway
Authors: Tianqi Lu, Ziqi Zhang, Zhenfei Bi, Tianxia Lan, Hao Zeng, Yu Liu, Fei Mo, Jingyun Yang, Siyuan Chen, Xuemei He, Weiqi Hong, Zhe Zhang, Ruyu Pi, Wenyan Ren, Xiaohe Tian, Yuquan Wei, Min Luo, Xiawei Wei
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Mitochondrial transcription factor A (TFAM) is a transcription factor that maintains mitochondrial DNA (mtDNA) stabilization and initiates mtDNA replication. However, little is known about the immune regulation function and TFAM expression in immune cells in the tumors. Methods Mouse tumor models were applied to analyze the effect of TFAM deficiency in myeloid cell lineage on tumor progression and tumor microenvironment (TME) modification. In vitro, primary mouse bone marrow-derived dendritic cells (BMDCs) were used in the investigation of the altered function and the activated pathway. OVA was used as the model antigen to validate the activation of immune responses in vivo. STING inhibitors were used to confirm the STING activation provoked by Tfam deficient in DCs. Results The deletion of TFAM in DCs led to mitochondrial dysfunction and mtDNA cytosolic leakage resulting in the cGAS-STING pathway activation in DCs, which contributed to the enhanced antigen presentation. The deletion of TFAM in DCs has interestingly reversed the immune suppressive TME and inhibited tumor growth and metastasis in tumor models. Conclusions We have revealed that TFAM knockout in DCs ameliorated immune-suppressive microenvironment in tumors through STING pathway. Our work suggests that specific TFAM knockout in DCs might be a compelling strategy for designing novel immunotherapy methods in the future.
Contaminated dicloxacillin capsules as the source of an NDM-5/OXA-48-producing Enterobacter hormaechei ST79 outbreak, Denmark and Iceland, 2022 and 2023
Authors: Charlotte Nielsen Agergaard, Lone Jannok Porsbo, Thomas Vognbjerg Sydenham, Sanne Grønvall Kjær Hansen, Kat Steinke, Sanne Løkkegaard Larsen, Kristján Orri Helgason, Frank Hansen, Kasper Thystrup Karstensen, Anna E Henius, Barbara Juliane Holzknecht, Lillian Søes, Kristian Schønning, Mikala Wang, Nina Ank, Anna Margrét Halldórsdóttir, Ólafur Guðlaugsson, Anette M Hammerum, Anne Kjerulf, Brian Kristensen, Henrik Hasman, Ulrik Stenz Justesen
Journal: Eurosurveillance (2023)

From October 2022 through January 2023, nine patients with NDM-5/OXA-48-carbapenemase-producing Enterobacter hormaechei ST79 were detected in Denmark and subsequently one patient in Iceland. There were no nosocomial links between patients, but they had all been treated with dicloxacillin capsules. An NDM-5/OXA-48-carbapenemase-producing E. hormaechei ST79, identical to patient isolates, was cultured from the surface of dicloxacillin capsules in Denmark, strongly implicating them as the source of the outbreak. Special attention is required to detect the outbreak strain in the microbiology laboratory.
Overcoming Barriers to Tumor Genomic Profiling through Direct-to-Patient Outreach
Authors: Seyram A. Doe-Tetteh, Sabrina Y. Camp, Dalicia Reales, Jett Crowdis, Anne Marie Noronha, Bernadette Wolff, Tina Alano, Jesse Galle, S. Duygu Selcuklu, Agnes Viale, Nicholas D. Socci, Ying L. Liu, William P. Tew, Carol Aghajanian, Marc Ladanyi, Meng Xiao He, Saud H. AlDubayan, Roei David Mazor, Ofer Shpilberg, Oshrat Hershkovitz-Rokah, Jose A. Riancho, Jose L. Hernandez, M. Carmen Gonzalez-Vela, Justin J. Buthorn, Manda Wilson, Amy E. Webber, Mariko Yabe, Kseniya Petrova-Drus, Marc Rosenblum, Benjamin H. Durham, Omar Abdel-Wahab, Michael F. Berger, Mark T.A. Donoghue, Andrew L. Kung, Julia Glade Bender, Neerav N. Shukla, Samuel A. Funt, Ahmet Dogan, Robert A. Soslow, Hikmat Al-Ahmadie, Darren R. Feldman, Eliezer M. Van Allen, Eli L. Diamond, David B. Solit
Journal: Clinical Cancer Research (2023)

Abstract Purpose: To overcome barriers to genomic testing for patients with rare cancers, we initiated a program to offer free clinical tumor genomic testing worldwide to patients with select rare cancer subtypes. Experimental Design: Patients were recruited through social media outreach and engagement with disease-specific advocacy groups, with a focus on patients with histiocytosis, germ cell tumors (GCT), and pediatric cancers. Tumors were analyzed using the MSK-IMPACT next-generation sequencing assay with the return of results to patients and their local physicians. Whole-exome recapture was performed for female patients with GCTs to define the genomic landscape of this rare cancer subtype. Results: A total of 333 patients were enrolled, and tumor tissue was received for 288 (86.4%), with 250 (86.8%) having tumor DNA of sufficient quality for MSK-IMPACT testing. Eighteen patients with histiocytosis have received genomically guided therapy to date, of whom 17 (94%) have had clinical benefit with a mean treatment duration of 21.7 months (range, 6–40+). Whole-exome sequencing of ovarian GCTs identified a subset with haploid genotypes, a phenotype rarely observed in other cancer types. Actionable genomic alterations were rare in ovarian GCT (28%); however, 2 patients with ovarian GCTs with squamous transformation had high tumor mutational burden, one of whom had a complete response to pembrolizumab. Conclusions: Direct-to-patient outreach can facilitate the assembly of cohorts of rare cancers of sufficient size to define their genomic landscape. By profiling tumors in a clinical laboratory, results could be reported to patients and their local physicians to guide treatment. See related commentary by Desai and Subbiah, p. 2339
Implication of<sup>99m</sup>Tc-sum IL-2 SPECT/CT in immunotherapy by imaging of tumor-infiltrating T cells
Authors: Yu Gao, Qi Luo, Zhichen Sun, Hannan Gao, Yue Yu, Yining Sun, Xiaotu Ma, Chuanhui Han, Jiyun Shi, Fan Wang
Journal: Journal for ImmunoTherapy of Cancer (2023)

Background Although immune checkpoint blockade (ICB) and adoptive T cell transfer (ACT) therapy have achieved impressive clinical outcomes, majority of patients do not respond to immunotherapy. Tumor-infiltrating T cells, a critical factor to immunotherapy, is dynamically changing. Therefore, a reliable real-time in vivo imaging system for tumor-infiltrating T cells, but not immunohistochemical analyses, will be more valuable to predict response and guide immunotherapy. In this study, we developed a new SPECT/CT imaging probe 99m Tc-sum IL-2 targeting the IL-2Rβ/IL-2Rγ (CD122/CD132) receptor on tumor-infiltrating T cells, and evaluated its application in predicting the immune response to anti-PD-L1 (αPD-L1) therapy as well as tracking infused T cells in ACT therapy. Methods The binding affinity of the super mutated IL-2 (sum IL-2) in various T cell subtypes was measured. Sum IL-2 was subsequently labeled with 99m Tc through Sortase-A mediated site-specific transpeptidation. SPECT/CT imaging and biodistribution studies of 99m Tc-sum IL-2 were performed in a MC38 mouse model. Wild type IL-2 (IL-2) was used as control in the above studies. Finally, we evaluated 99m Tc-sum IL-2 SPECT/CT for the detection of tumor-infiltrating T cells in the context of αPD-L1 immunotherapy and ACT therapy. Results Sum IL-2 preferentially bound to CD8 + T cells, especially activated CD8 + T cells, while IL-2 showed biased binding to Treg cells. As a result, 99m Tc-sum IL-2 could detect tumor-infiltrating T cells. In the MC38 tumor model, SPECT/CT imaging showed the increased tumor uptake of 99m Tc-sum IL-2 after αPD-L1 treatment, suggesting that the treatment significantly increased tumor-infiltrating T cells, resulting in a correspondingly significant curative effect. In addition, 99m Tc-sum IL-2 SPECT/CT could also track the infiltration of antigen-specific cytotoxic CD8 + T cells during ACT therapy. Conclusion 99m Tc-sum IL-2 has great clinical potential for non-invasive and specific SPECT/CT imaging of tumor-infiltrating T cells as well as for timely prediction and evaluation of the therapeutic efficacy of ICB and ACT therapy.
Anti–Neutrophil Extracellular Trap Antibodies in Antiphospholipid Antibody–Positive Patients: Results From the Antiphospholipid Syndrome Alliance for Clinical Trials and <scp>InternatiOnal</scp> Networking Clinical Database and Repository
Authors: Yu Zuo, Sherwin Navaz, Alex Tsodikov, Katarina Kmetova, Lyndsay Kluge, Amala Ambati, Claire K. Hoy, Srilakshmi Yalavarthi, Danieli de Andrade, Maria G. Tektonidou, Savino Sciascia, Vittorio Pengo, Guillermo Ruiz‐Irastorza, H. Michael Belmont, Maria Gerosa, Paul R. Fortin, Guilherme Ramires de Jesus, D. Ware Branch, Laura Andreoli, Esther Rodriguez‐Almaraz, Michelle Petri, Ricard Cervera, Rohan Willis, David R. Karp, Quan‐Zhen Li, Hannah Cohen, Maria Laura Bertolaccini, Doruk Erkan, Jason S. Knight
Journal: Arthritis & Rheumatology (2023)

This study aimed to elucidate the presence, antigen specificities, and potential clinical associations of anti-neutrophil extracellular trap (anti-NET) antibodies in a multinational cohort of antiphospholipid (aPL) antibody-positive patients who did not have lupus.
Validation of the prognostic significance of the 2022 European <scp>LeukemiaNet</scp> risk stratification system in intensive chemotherapy treated aged 18 to 65 years patients with de novo acute myeloid leukemia
Authors: Min‐Yen Lo, Xavier Cheng‐Hong Tsai, Chien‐Chin Lin, Feng‐Ming Tien, Yuan‐Yeh Kuo, Wan‐Hsuan Lee, Yen‐Ling Peng, Ming‐Chih Liu, Mei‐Hsuan Tseng, Cheng‐An Hsu, Jui‐Che Chen, Liang‐In Lin, Hsun‐I Sun, Yi‐Kuang Chuang, Bor‐Sheng Ko, Jih‐Luh Tang, Ming Yao, Wen‐Chien Chou, Hsin‐An Hou, Hwei‐Fang Tien
Journal: American Journal of Hematology (2023)

The European LeukemiaNet (ELN) recently proposed a revised recommendation for the diagnosis and management of acute myeloid leukemia (AML) in adults, recognized as ELN-2022. However, validation in a large real-world cohort remains lacking. In this study, we aimed to validate the prognostic relevance of the ELN-2022 in a cohort of 809 de novo, non-M3, younger (ages 18-65 years) AML patients receiving standard chemotherapy. The risk categories of 106 (13.1%) patients were reclassified from that determined using ELN-2017 to that determined using ELN-2022. The ELN-2022 effectively helped distinguish patients as favorable, intermediate, and adverse risk groups in terms of remission rates and survival. Among patients who achieved first complete remission (CR1), allogeneic transplantation was beneficial for those in the intermediate risk group, but not for those in the favorable or adverse risk groups. We further refined the ELN-2022 system by re-categorizing AML patients with t(8;21)(q22;q22.1)/RUNX1::RUNX1T1 with KIThigh , JAK2 or FLT3-ITDhigh mutations into the intermediate risk subset, AML patients with t(7;11)(p15;p15)/NUP98::HOXA9 and AML patients with co-mutated DNMT3A and FLT3-ITD into the adverse risk subsets, and AML patients with complex or monosomal karyotypes, inv (3)(q21.3q26.2) or t(3;3)(q21.3;q26.2)/GATA2,MECOM(EVI1) or TP53 mutation into the very adverse risk subset. The refined ELN-2022 system performed effectively to distinguish patients as favorable, intermediate, adverse, and very adverse risk groups. In conclusion, the ELN-2022 helped distinguish younger, intensively treated patients into three groups with distinct outcomes; the proposed refinement of ELN-2022 may further improve risk stratification among AML patients. Prospective validation of the new predictive model is necessary.
<i>Cronobacter sakazakii</i> Infections in Two Infants Linked to Powdered Infant Formula and Breast Pump Equipment — United States, 2021 and 2022
Authors: Julia C. Haston, Shanna Miko, Jennifer R. Cope, Haley McKeel, Cynney Walters, Lavin A. Joseph, Taylor Griswold, Lee S. Katz, Ashley A. Andújar, Laura Tourdot, Joshua Rounds, Paula Vagnone, Carlota Medus, JoAnn Harris, Robert Geist, Daniel Neises, Ashley Wiggington, Trey Smith, Monica S. Im, Courtney Wheeler, Peyton Smith, Heather A. Carleton, Christine C. Lee
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Genomic DNA was extracted and sequenced on MiSeq instruments (Illumina) following Nextera XT or DNA Prep
First-line Systemic Treatment Options for Metastatic Castration-Sensitive Prostate Cancer
Authors: Irbaz Bin Riaz, Syed Arsalan Ahmed Naqvi, Huan He, Noureen Asghar, Rabbia Siddiqi, Hongfang Liu, Parminder Singh, Daniel S. Childs, Praful Ravi, Syed A. Hussain, Mohammad Hassan Murad, Stephen A. Boorjian, Christopher Sweeney, Eliezer M. Van Allen, Alan H. Bryce
Journal: JAMA Oncology (2023)

The effectiveness of triplet therapy compared with androgen pathway inhibitor (API) doublets in a heterogeneous patient population with metastatic castration-sensitive prostate cancer (mCSPC) is unknown.
“Massive relief” as Northern Ireland’s health sector embraces Windsor framework
Authors: Chris Baraniuk
Journal: BMJ (2023)

After years of post-Brexit precariousness the Windsor framework has more or less "solved" the question of how medicines will continue to flow into Northern Ireland from Great Britain, health experts have said.Until this week pharmaceutical suppliers in Great Britain faced increased costs for relabelling medicines destined for Northern Ireland under the Northern Ireland protocol, which forms part of the Brexit withdrawal agreement signed by the UK and the European Union in 2020.